ALKBH5-mediated m6A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis

Cell Death Dis. 2022 Nov 5;13(11):926. doi: 10.1038/s41419-022-05386-4.

Abstract

As the most important RNA epigenetic regulation in eukaryotic cells, N6-metheyladenosine (m6A) modification has been demonstrated to play significant roles in cancer progression. However, this modification in long intergenic non-coding RNAs (lincRNAs) and the corresponding functions remain elusive. Here, we showed a lincRNA LINC02551 was downregulated by AlkB Homolog 5 (ALKBH5) overexpression in a m6A-dependent manner in hepatocellular carcinoma (HCC). Functionally, LINC02551 was required for the growth and metastasis of HCC. Mechanistically, LINC02551, a bona fide m6A target of ALKBH5, acted as a molecular adaptor that blocked the combination between DDX24 and a E3 ligase TRIM27 to decrease the ubiquitination and subsequent degradation of DDX24, ultimately facilitating HCC growth and metastasis. Thus, ALKBH5-mediated LINC02551 m6A methylation was required for HCC growth and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AlkB Homolog 5, RNA Demethylase / genetics
  • AlkB Homolog 5, RNA Demethylase / metabolism
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / pathology
  • DEAD-box RNA Helicases / metabolism
  • Epigenesis, Genetic
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • RNA, Long Noncoding
  • AlkB Homolog 5, RNA Demethylase
  • DDX24 protein, human
  • DEAD-box RNA Helicases
  • ALKBH5 protein, human